Vitamin K in brain metabolism and cognitive function: mechanistic evidence, human associations, and unresolved questions.

Abstract

Vitamin K acts as a critical regulator across diverse biological systems, contributing significantly to skeletal integrity, cardiovascular functions, metabolic homeostasis, and immune defenses. Experimental studies increasingly suggest that it also plays an important role in the nervous system, supporting neuronal growth, differentiation, and survival. Its antioxidant, anti-inflammatory, and antiapoptotic effects, along with its capacity to act as an alternative electron carrier in mitochondria, further indicate potential neuroprotective properties. This narrative review synthesizes evidence from recent cell and animal studies, mechanistic research on sphingolipid metabolism, and observational data evaluating vitamin K status and cognitive outcomes. Findings from populations receiving long-term vitamin K antagonist therapy were reviewed to highlight potential clinical implications. Regulation of sphingolipid pathways by vitamin K appears to support neuronal proliferation and resilience, while adequate vitamin K levels have been associated with better cognitive performance. Conversely, prolonged exposure to vitamin K antagonists has been linked to impairments in visual memory and verbal fluency, as well as reductions in brain volume. Evidence also indicates that vitamin K is essential for the synthesis and maintenance of myelin and neuronal membrane components, and for activating vitamin K-dependent proteins that preserve neuronal integrity. Beyond its established role in coagulation, emerging preclinical and observational evidence suggests that vitamin K may possess neuroprotective potential through molecular, structural, and antioxidant mechanisms. The observed association between vitamin K antagonist therapy and cognitive decline in older adults highlights the need for comprehensive clinical studies to clarify causality, determine therapeutic relevance, and better define the role of vitamin K in brain health.